Abstract
The voltage-dependent potassium channel Kv7.1 assembles with the KCNE1 regulatory subunit recapitulating the cardiac IKs currents. Although the Kv7.1/KCNE1 complex receives much attention, the subcellular compartment hosting the interaction is the subject of intense debate. Two alternative hypothesis have been raised. Thus, the complex forms either earlier in the endoplasmic reticulum or directly at the plasma membrane. The importance of such issue is confirmed by Kv7.1 and KCNE1 mutations, responsible for long-QT syndromes, which impairing association and traffic alter IKs currents. Our work demonstrates that Kv7.1 and KCNE1 do not interact in the first stages of their biogenesis. Data support an unconventional secretory pathway for Kv7.1-KCNE1 that bypasses Golgi. This forward trafficking route drives channels to endoplasmic reticulum-plasma membrane junctions (ER-PM), where the Kv7.1-KCNE1 complex assembles. This mechanism helps to resolve the ongoing controversy about the subcellular compartment hosting the association. Our results provide new insights into IKs channel localization at ER-PM junctions, deciphering an alternative anterograde trafficking route for oligomeric ion channels.Supported by BFU2017-87104-R from the Ministerio de Economia y Competitividad (MINECO, Spain) and Fondo Europeo de Desarrollo Regional (FEDER).
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